BOTULINUM A TOXIN THERAPY - NEUTRALIZING AND NONNEUTRALIZING ANTIBODIES-THERAPEUTIC CONSEQUENCES

Although muscle-relaxant doses of botulinum A toxin (BoNT/A) are gener ally lower than doses stimulating the immune system, specific antibodi es are raised in a substantial number of patients. As a rule, this nec essitates the termination of treatment. Therefore, a reliable determin ation of specific anti-BoNT/A antibodies is helpful and we introduced, for this purpose, a novel in vitro toxin-neutralizing assay based on a nerve-muscle preparation. We measured the antibody titers in four gr oups of subjects: Group 1 comprised 75 randomly selected patients of a total of 295 who responded to treatment with Dysport in our local cli nic. Five patients, in group 2, were nonresponders. Group 3 consisted of 32 untreated volunteers and group 4 of 8 subjects immunized with a toroid more than 10 years ago. Two of the responders had marginal tite rs of neutralizing antibodies, while they were present in all nonrespo nders. The sera of all responders were also tested for nonneutralizing antibodies by ELISA. Their occurrence, however, was of no consequence to the therapeutic success. The blood samples of volunteers were free from specific antibodies, whereas antibodies persisted in the immuniz ed subjects for longer than a decade. Patients from various clinics wh o had been treated unsuccessfully with the toxin-14 patients had recei ved BOTOX, 7 had been treated with Dysport, and 7 with both products-a ll had neutralizing antibodies. Whether there was an antibody response depended on the amount of toxin administered. We believe, however, th e effective toxin dose can be reduced by so much as to make antibody p roduction highly improbable. (C) 1997 Academic Press.